2009 Pandemic H1N1 Influenza

01/06/2014

The National Infectious Disease Forecast Center has received several inquiries regarding H1N1 influenza activity in the US this season. Here we would like to share our observations:

The National Infectious Disease Forecast Center publicly forecasted anticipation of an A/H1N1-dominant season with excellent vaccine match beginning in August. Expectation was that it would be a mild season.

Thus far, physicians and infection control practitioners directly involved with patient care of H1N1 cases in Mexico, the US, and Canada have unanimously indicated ICU admissions and fatalities are seen in unvaccinated patients. In a minority of cases, they are unclear about vaccination history.

All H1N1 isolates submitted to CDC have matched this season's vaccine strain based on reporting from Week 52. At a national level, the overall picture of the season is mild/moderate. There is a slight inflexion of the epi curve reported in Week 52. We are hopeful this is indicative of peaking out, however prior seasons have shown a similar brief inflexion before additional case surge. Obviously, monitoring subsequent reports will shed more light on where we are going with this.

It is our belief that, from the perspective of those individuals who have chosen not to vaccinate for this year's influenza, we are basically seeing another pandemic wave of H1N1 transmission with the associated potential for severe clinical outcomes. For those who are vaccinated, the experience is a mild one.

Point #4 highlights a bit of irony for our team, where we are attempting to forecast certain features of the influenza season. What we have found is the possibility of anti-vaccination politics playing a major role in interfering with the validation of our forecast. We have observed through direct clinical experience that anti-vaccination sentiment, particularly for influenza, remains strong in the US and are tied to politics. It is clear to those of us monitoring the situation that such views have a mortality rate.

01/08/2012

If one examines every CDC Flu Weekly report since the 1997-1998 season, one notices stretches of editorial errors and careless data transcription in the early years. It is almost as if those filling out the reports intuitively knew most people didn't bother to read the deeper complexity of the information- specifically that describing antigenic testing and compatibility with vaccine strains.

After SARS, H5N1 emergence in Asia, and the 2009 H1N1 influenza pandemic, many more are paying attention to the information. Here in Operational Biosurveillance and elsewhere people noticed the emergence of A/H3N2v being reported and viewed it as an opportunity to tell CDC "here's your chance to make right". Indeed that appears to be happening, with seed stock being moved to the vaccine manufacturers and very quickly thereafter movement to clinical trials. These are good measures of progress for an agency we've grown quite frustrated with over the years.

We are pleased to finally see guidance for clinicians trying to make the difficult decision in the context of an economic recession whether to test for influenza in their patients (i.e. children):

Currently, while there are low levels of circulating seasonal influenza viruses, CDC recommends increasing collection of specimens from patients with influenza-like illness (ILI) , and having these specimens sent to the state or local laboratory for prioritization for rRT-PCR testing. States should specifically consider increasing collection of specimens from patients presenting with ILI in the following high priority areas:

ILI outbreaks, particularly among children in child-care and school settings, since these have been the settings associated with human-to-human influenza A(H3N2)v virus transmission.

Unusual or severe presentations of ILI, especially among children.

Medically attended ILI and ARI in children under 18 years of age

Our only nit-pick with the recommendations (albeit an important one) is to suggest that pediatricians should at least test medically attended ILI and ARI in children under 18 years of age who were vaccinated for this season's influenza. This is a loose call at this point given the low number of cases identified so far, however it may overcome social reluctance to test.

We have pinged several physician and pediatric social networks to raise this issue to their attention- that testing children with influenza-like illness may enable quicker decision-making for response. That we have an opportunity to shorten the time delta to having a vaccine if we need it for our patients. However we still see "pandemic fatigue" and desensitization to anything related to the word "pandemic". And yes, with all the talk of healthcare spending cuts physicians do appear to hesitate to test for fear of denial of coverage by insurance. In our patient population, we hesitate to test because our patients are at poverty level already, without insurance, without Medicaid, and may be paying in cash. Often these are our sickest patients and the very ones we should test.

But this entire phenomenon of holding public health accountable for faster reporting of A/H3N2v, transparency in the decision process to move vaccine through trials just in case, and enhanced media visibility to, let's face it, a bare few cases that would have escaped notice just a few short years ago. Technology does make us more vulnerable because we don't have as much ignorance to be blissful about. But social media holds us nevertheless responsible for this information and the actions implied by that information. One only needs to see the hashtag "H3N2" on Twitter to see the wave of social sensitization.

Here we are hopeful that the convergence of better laboratory diagnostics, risk communication, transparency in response operations, and the accountability provided by social media brings positive change in public health. And positive change improves our nation's resilience in the face of infectious disease crises.

12/29/2011

For the last 15 or so years, we have seen an explosion of different electronic disease surveillance systems emerge. Everything from laboratory diagnostics and reporting systems to syndromic surveillance to using the internet for so-called "event-based surveillance". And there has been a virtual orgy of academic frenzy around the "bright lights and shiny object" effect of the technology. This is representative of billions of taxpayer dollars over these years dispensed from a variety of federal mechanisms.

Yet, with all of this expenditure (much of which is ongoing), we have still so very little proof of operational value. The "research and development ice cream cone" continues to lick itself without any apparent metric held by the funders for the operational "so what". Arthur Reingold's challenge points from 2003 still appear to be unanswered ten years later. Below, his points have been adjusted to fit a more broad consideration of the topic:

Circumstances under which [x, y, z type of] surveillance is likely to strengthen local and state health departments.

Certainly Reingold was not the only person during the heyday of syndromic surveillance to raise questions about the validity of the approach, but the gist of the above challenges were echoed several times in the literature. But the academics lept onward undeterred, and the marketing associated with their programs grew to astounding levels of claimed accomplishments.

One such claim was that made by John Brownstein of HealthMap on Aug 3rd at an IARPA OSI Program Proposer's Day, who stated (paraphrased) that HealthMap was "the first surveillance system in the world to detect and publicly report the 2009 H1N1 influenza pandemic". This impressive claim invokes scrutiny into the defintion of detection and how it applies to evaluating any disease surveillance system... and of course, the taxpayer funds associated with that program.

However it is the word's Latin origin, cognoscere that brings this point into focus. Cognoscere means to know. Of course the word know implies that a human being's mental processes have been engaged. Which implies 1) there is a human being looking at the data and thinking about it.

So this implies a human being, having thought about the data, has recognized and prioritized a concern... and communicated that specific concern to others.

The analytic team that warned the senior health intelligence officer in CDC's Director's Emergency Operations Center (DEOC) noted at the time that HealthMap's information was 1) not posted on their website as fast as the original Mexican source posting 2) was not highlighted in any unusual way to call singular attention to the information among dozens (hundreds?) of other colored pins on their map, and 3) where was no transfer of information to ProMED or CDC from HealthMap evident to suggest that human beings had communicated about the information during early to mid April 2009. Therefore, the following may be concluded:

The first point of detection was actually the Mexican journalist who wrote the first article on the La Gloria situation. HealthMap simply functioned as a Google News parser- a function anyone could have performed using Google Alerts. If you happened to click that one pin on the map, you would have 'seen' the report, albeit then you would have to understand whether what was being reported was unusual...

Human beings were required to recognize unusual indicator patterns in the initial reports (n=1 to 3), not through recognition of simply volume of reporting as captured by HealthMap's Heat Index.

Human to human communication clearly had to occur to push the warning through, as information provided via pull websites and push email notifications were inadequate due to daily information overload at WHO and CDC.

The point of the above is not to singularly criticize HealthMap but to make a point: collection of data is insufficient, by itself, to generate operational impact. This was a very hard lesson learned by the syndromic surveillance community as well. And if you are fighting an embedded, decades-old professional culture imbued with a "not invented here" bias (i.e. public health), it is unlikely the data will be exploited properly.

So let's give Brownstein a break for a minute and focus on one of his collaborators: the Canadian Global Public Health Network (GPHIN). Brownstein's claim at the IARPA meeting was a duplication of GPHIN's claim to the world of having been the first public health system to detect SARS (see attached manuscript, Figure 1). However there was unverified rumor at the time that the web-harvested Chinese media article published on Nov 27, 2002 went unnoticed by GPHIN's staff for some time due to lack of machine translation for Chinese (unverified) and lack of a Chinese linguist. Even if these rumors were false, and GPHIN's system immediately punched a warning out to its customers, there is no evidence anyone was paying attention. In the multiple manuscripts and powerpoints given by GPHIN staff, not one contains copies of emails or phone records to indicate human beings had 1) recognized the problem, 2) prioritized the problem (out of the dozens of other reports for the day), and 3) communicated directly with the Canadian PHAC, the US CDC, or WHO specifically about this prioritized problem. This is concerning when considering how much information was actually missed at the time (see attached report by Polyak et al).

The analogy is football: it's like being thrilled you threw a "Hail Mary" pass, but unawares that 1) no one caught the ball and 2) ran it to the end zone... 3) and thus you lost the game in the process. Sound familiar? It should. These are very similar issues to those in the original 9/11 Commission Report.

Currently the federal government continues to chase its tail, spending more funds on biosurveillance research: the self-licking ice cream cone. Billions of dollars and 10-15 years later, we still are not holding these systems' collective feet to the fire asking "show me don't tell me". We continue to reach for the bright lights and shiney objects represented by the latest fad technology ("social media" being the current one) without thinking about how to promote the human process of understanding the data, accumulating knowledge, and using that knowledge to impact the potential outcome of the threat.

12/25/2011

On December 23rd, CDC released another statement about the evolving situation with swine-origin triple reassortant influenza A(H3N2) virus in the United States. Three more human infections, two of which associated with a daycare in West Virginia. The latter is of greater concern than the former due to probable human-human transmission. Time delays between submission of samples and public report by CDC remain high:

... No further information regarding when West Virginia's state laboratory or CDC processed the sample, which was A(H3N2)v-positive.

Summary:

Time delta: state public health recognition of unusual virus= unknown

Time delta: clinical processing of patient to CDC awareness= unknown

Time delta: CDC issuance of warning to the public= 34 days from initial clinical processing of the patient (approx. Nov 19th)

(Case C) West Virginia, same cluster / thread.

Day 0 (Nov 29th). 2nd child at daycare center ill.

Day 9 (Dec 7th). West Virginia Office of Laboratory Services processes sample as "inconclusive"- forwards on to CDC. This patient was part of a retrospective assessment, where clinical processing did not occur.

.. No further information regarding when CDC processed the sample, which was A(H3N2)v-positive.

Summary:

Time delta: CDC issuance of warning to the public= 34 days from state public health laboratory processing of the sample to CDC issuance of public warning

The key point is of course, we only know what we are able to know. Our team leaned into the discussion in November to ensure CDC was aware we were 1) monitoring the situation and 2) are carefully documenting their performance in coupling warning to response. And quietly behind the scenes we are engaging clinical practitioners in an effort to encourage more sampling among symptomatic patients who were vaccinated for this season. We expect the predominance of this focus to be on pediatric patients, however we are not seeing social sensitization yet among pediatricians. Messaging from CDC requires clarification and guidance regarding when to sample.

Currently, we are observing between large time deltas between clinical processing of these patients and CDC's issuance of public warning. It is our opinion that if A(H3N2)v suddenly displaces current seasonal A/H3N2 or gains significant prevalence, the first point of recognition may be an abruptly overwhelmed pediatric medical infrastructure versus dramatically time-delayed reporting from CDC.

The observations of public health performance during the 2009 influenza pandemic begin to repeat themselves...

The prioritization and distribution of
vaccine in future influenza pandemics should be reexamined.

Improvements are needed in the healthcare
response to a large-scale bioterrorism attack.

The role of disease containment measures
in the response to a SARS-like emerging infectious disease should be
reconsidered.

Unfortunately, there was no focus on the front-end piece, the one piece essential to response: an effective biological threat detection and warning system.

As one of the original group of individuals who called for the creation of the National Biosurveillance Integration Center (then called the "National Biosurveillance Integration System") under HSPD-7, -9, -10, NSPD-33, and Public Law 110-53, it is disheartening to see criticism of a key component of our nation's security apparatus without engaging in open discussion with those who have professional experience in operational biosurveillance:

What is also required is an effective operational bridge between early warning and response. When we briefed ASPR/HHS several months before the 2009 H1N1 influenza pandemic, Dr. Vanderwagen admitted (paraphrased), "even if we had credible warning of an influenza pandemic, we wouldn't know what to do with it." I respected him greatly for his candor. It is unfortunate we made no further progress in the dialog in the months before the pandemic.

There actually was a strategy to NBIC, and one that was vetted with every federal agency with an operational stake in biodefense at the original Concept Design Review meetings. But there was minimal support inside DHS
to implement the program properly and other federal agencies refused to
share information with the nascent center. It was a sociological
problem first and foremost. And Machiavellian. Nearly identical
challenges and contention in implementing this concept as the
idea of storm forecasting in the 1800s. Same kind of bickering and
fighting among academics, politicians, and bureaucrats over control of
operationalization of the concept that winds up delaying effective
realization of a public benefit by decades.

In a recent testimony by Dr. Alex Garza, NBIC "provided critical biosurveillance information... on the 2009 H1N1 influenza pandemic". It would be helpful to understand the definition of "critical" along with a full review of what early warning information was recognized by NBIC analysts and conveyed to decision makers in the form of a warning.

Our experience during the pandemic was quite revealing. The timeliness issues with CDC have already been discussed here. The broader public health community generally did not promote informal surveillance processes to share information. With but two notable exceptions, none of the federally-funded public health and healthcare professional organizations we engaged (and we approached all of them) shared situational awareness information during the pandemic. Federal, state, and local authorities pleaded for access to our information but wound up rarely ever sharing information or answering questions about reports in their areas of responsibility. The public would be quite surprised to see the email transcripts during the early days of the crisis of us admonishing public health organizations to share information.

Those that rose to the occasion were individual healthcare providers, and they were heroic in their efforts to be appropriately transparent about medical grid loading and strain, anxiety levels of staff, and unusual clinical findings without compromising patient privacy. This is how we were able to detect events and event features more quickly than official communication channels. Indeed, during the emergence of the pandemic, conversation with public health officials became operationally irrelevant.

We are observing a similar phenomenon in Haiti, where the major multi-million dollar NGOs are not readily engaging in informal information sharing about disease incidence. However, smaller more agile humanitarian groups and individual responders are.

Our conclusion from these experiences is the bigger and more complex the organization, the less able it is to share critical information in a timely fashion during crises and disasters.

Our team has demonstrated the feasibility of issuing
timely warning information for biological events such as:

- Near-real time operational biosurveillance support to the 2004 tsunami disaster
response theater

- Detection of SARS laboratory accident in Taiwan (2004)

- Detection of Marburg hemorrhagic fever in Angola for the first
time in history (2005)

- Detection of streptococcus suis in swine and humans in China
(2005)

- Detection of PRRS in swine in China with subsequent impact on
global heparin production (2005)

- The spread of H5N1 avian influenza in Asia, Europe, and Africa
(2005 and 2006)

- Detection of Ebola hemorrhagic fever outbreaks in Africa

- First forecast and detection of Rift Valley fever in East Africa
(2006)

Improvements in biological threat warning have actually occurred, and a professional discipline has now been present for several years now. We openly invite decision makers to engage people with operational experience dealing with these issues as soon as possible before the next infectious disease crisis presents itself.

03/28/2010

On March 26th, the Chilean Ministry of Health reported
the first confirmed case of pandemic H1N1 influenza among earthquake-affected populations.The infected is a five-year-old male from Mocha
Island who is currently receiving treatment at Guillermo Grant Benavente
Hospital located in Concepción.In response, the Ministry is reported
to be expanding influenza vaccinations among risk groups and individuals living
in temporary shelters.

In our Initial Operational
Biosurveillance Assessment of Chile following the February 27th earthquake,
we noted an increased risk of pandemic H1N1 influenza transmission once
conditions are optimized.Daily-recorded
temperatures in Concepción are transitioning to conditions favorable for
increased transmission of influenza viruses and should be optimized in the
coming weeks making current vaccination campaigns a key response measure.

02/12/2010

In a recent article by Sprung et al in the journal Intensive Care Unit, the European Society of Intensive Care Medicine presented their summary recommendations for intensive care unit triage during an influenza epidemic or mass disaster. I offered a response to the authors based on our experience during the emergence of pH1N1 in Mexico:

I read your paper titled “Recommendations for intensive care unit and hospital preparations for an influenza epidemic or mass disaster: summary report of the European Society of Intensive Care Medicine’s Task Force for intensive care unit triage during an influenza epidemic or mass disaster“ with great interest.

Attached please find a paper we published a couple of months prior to the H1N1 pandemic. We provided warning of the Mexico crisis to CDC and WHO and later created a near-real time situational awareness feed for the Society of Critical Care Medicine and the Critical Care Medicine- and Virtual PICU Listservs (CCM-L and vPICU) during the subsequent pandemic waves.

Your recommendations were spot-on except for one crucial point: an adequate early warning system for intensive care units. Infectious disease crises and disasters must be detected, warned, and proactively acted upon by those members of the medical community most impacted. I have also attached the experience of Vancouver versus Toronto during SARS- a tale of cities that presents an important perspective about the value of forewarning.

It was long our considered assessment the emergency department-intensive care unit axis of a hospital in developed nations represents the single most important part of the medical infrastructure. And most specifically, it is the intensive care unit we were most concerned about. This reasoning was due to

The fragile nature of multiple ICUs functioning as a grid in the urban environment- and how easily it may be overwhelmed.

Public expectation for uninhibited access to a given standard of care and changes in social anxiety levels once it is known the local capacity for critical care treatment has been grossly exceeded- especially in the pediatric setting.

The socio-economic disruption related to loss of a critical care facility in an urban setting was apparent in Hong Kong and Toronto during SARS. We in the United States have been fortunate to have so many “near misses”.

Infrastructure resiliency is directly related to forewarning and length of forewarning coupled to a practiced understanding of what to do upon receiving a warning. Our experience during the 2009 H1N1 influenza pandemic showed both the Society for Critical Care Medicine (SCCM) and the critical care community writ large to be impressively responsive, proactive, and quite willing to share information for the benefit of all involved as we assessed the changing features of the pandemic crisis. They represented the highest standard of biosurveillance information sharing we observed during the crisis among all (20+) of the professional disciplines we approached. I cannot commend the international critical care community more highly for their selfless actions to support situational awareness.

I recommend building upon these valuable lessons learned and capitalizing on the powerful strengths of this unique community of physicians to marry effective infectious disease crisis and disaster warning to response to protect this critical component of our medical infrastructure: the intensive care unit.

02/01/2010

Interesting. Reports coming in of pH1N1 pneumonia cases being replaced by streptococcal and staphylococcal pneumonia with severe presentations in Canada. It should be noted that strep and staph pneumonias are certainly seen in the critical care setting as a routine occurrence. What is less routine is several intensivists bothering to mention it at the same time from different locations.

Received report from intensivist in the UK talking about a "run of pneumococcal meningitis [they've] not seen in years". Temperature spike in one of the patients discussed above hit a whopping 109 degrees F. Speculation whether this phenomenon is somehow related to pH1N1.

01/27/2010

As expected, pH1N1-related hospital admissions have spiked- in Memphis they are seeking an increase in pediatric cases at Le Bonheur Children's Medical Center (18 patients since the first of the year). This is nearly the exact same moment (late January) resurgence of A/H2N2 was noted in the example we provided in a prior post. Vaccinations here are critical to avoid the potential of a pH1N1 / RSV epidemic curve overlap that could strain the pediatric medical infrastructure- particularly the pediatric intensive care units. Current reporting from pediatric intensivists suggest they are finding this to be a "bad" year for RSV:

"Besides being a bad RSV year, we seem to be seeing a new phenotype: term kids without any suggestion of chronic lung disease with severe small airway obstruction that is very responsive to bronchodilators. Seems very different in terms of duration of ventilation and response to bronchodilators than anything I've seen in the past."